We are studying mutant bacteria that are restrictive for growth of bacteriophage T4 and phage mutants that overcome restriction. At present, we are studying a collection of about 60 independently isolated rifampicin-resistant mutants of Escherichia coli that have lost ability to support phage infection while acquiring drug-resistance. We have isolated at least one unrestricted phage mutant for each of the bacterial strains. The locations of the phage and bacterial mutations will be determined by standard mapping experiments. The mechanisms of phage restriction will be studied by examining patterns of DNA and protein synthesis in phage-infected cells under restrictive conditions.